Senescent cells accumulate in aged organisms and promote the progression of age-related diseases including
cataracts. Therefore, we aimed to study the
therapeutic effects of senescence-targeting drugs on
cataracts. In this study, a 28-day
D-galactose-induced
cataract rat model was used. The opacity index, a grading based on
slit-lamp observations, was used to assess lens cloudiness. Furthermore, the average lens density (ALD), lens density standard deviation (LDSD), and maximum lens density (MLD) obtained from Scheimpflug images were used to assess lens transparency. Immunohistochemical stainings for p16 and γH2AX were used as hallmarks of senescence. We treated rat
cataract models with the senolytic
drug combination dasatinib plus
quercetin (D+Q) and senescence-associated secretory phenotype (SASP) inhibitors. In comparison to control
lenses,
D-galactose-induced
cataract lenses showed a higher opacity index, ALD, LDSD, and MLD values, as well as accumulation of senescent lens epithelial cells (LECs). After D+Q treatment, ALD, LDSD, and MLD values on day 21 were significantly lower than those of vehicle-treated model rats. The expression levels of p16 and γH2AX were also reduced after D+Q administration. In addition, the SASP inhibitor
rapamycin decreased the opacity index, ALD, LDSD, and MLD values on day 21. In conclusion, D+Q alleviated
D-galactose-induced
cataract progression by reducing the senescent LEC burden in the early stage of
cataract.